# Regulation of zinc-dependent lysosome morphological restructuring, zinc trafficking and low zinc homeostasis in C. elegans and human model systems

> **NIH NIH K99** · WASHINGTON UNIVERSITY · 2022 · $100,000

## Abstract

Project Summary/Abstract
Dysregulation of zinc homeostasis can lead to either zinc deficiency or zinc excess, resulting in a variety of
human pathologies. Therefore, strict regulation of zinc trafficking and storage are essential for cellular function
and human health. Robust studies of zinc biology can be conducted with a variety of model systems, and I
propose to combine the genetic and experimental power of Caenorhabditis elegans with the medical relevance
of human cell culture to develop a detailed and useful understanding of zinc biology. Studies from my early
postdoctoral training have uncovered that lysosome-related organelles, called gut granules in C. elegans, are
restructured in a zinc dependent manner; I identified an expansion compartment that increases in volume in zinc
excess and deficient conditions. In addition, the low zinc homeostasis pathway appears to be conserved in C.
elegans and humans, since the Low Zinc Activation enhancer element has been identified in the promoters of
zinc transporters that function the low zinc response in both organisms. To build upon these preliminary results,
I propose to take a multidisciplinary approach to understand how low zinc homeostasis is regulated and how
lysosomes are restructured. In Aim 1, I propose to characterize the zinc-dependent expansion compartment and
the membrane architecture of intestinal gut granules in C. elegans. In Aim 2, I will elucidate the regulation of zinc
trafficking and morphological restructuring of human lysosomes. In Aim 3, I will characterize the regulation of the
low zinc pathway in C. elegans and human cells.
This proposal will capitalize on my experience with interdisciplinary techniques from cell biology, chemistry, and
X-Ray physics, and expand upon them to complete my toolkit for probing zinc in biology with genetics and
biochemistry. Furthermore, I will expand into human cells as a model system. The training will also build upon
my extensive experience in science advocacy and equip me to be a powerful advocate for historically
marginalized groups as a faculty member. My training in the K99 phase will integrate the expertise from my
mentor Dr. Kornfeld and co-mentor Dr. Diwan to complete my preparation for the R00 independent phase.
Training during the K99 phase will integrate the experience from my mentors, collaborators, and advisory board
members to springboard my career as a scientist and science activist.
My long-term career goal is to lead a team of diverse trainees performing cutting edge techniques to probe critical
questions in zinc homeostasis and trafficking. I have a strong record demonstrating my abilities as a scientist,
and therefore my potential as a primary investigator. I am committed to conducting leading edge science AND
promoting institutional change to promote diversity and inclusion in academia. The K99/R00 award will maximize
my chances of being able to achieve my goals by providing critical resources and connections that would be
ot...

## Key facts

- **NIH application ID:** 10429846
- **Project number:** 1K99GM146016-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Adelita D. Mendoza
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $100,000
- **Award type:** 1
- **Project period:** 2022-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10429846

## Citation

> US National Institutes of Health, RePORTER application 10429846, Regulation of zinc-dependent lysosome morphological restructuring, zinc trafficking and low zinc homeostasis in C. elegans and human model systems (1K99GM146016-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10429846. Licensed CC0.

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